The correlation between sub-epidermal moisture assessment and other early indicators of pressure ulcer development: A prospective cohort observational study. Part 2. The correlation between sub-epidermal moisture assessment, temperature, epidermal hydration and pain.

There is growing interest in the roles of temperature, epidermal hydration (EH) and pain in pressure ulcer (PU) development. Investigating correlations between these measures and sub-epidermal moisture (SEM) will address this knowledge deficit. A prospective observational study enrolled 60 surgical patients from February to November 2021. SEM, temperature, EH and pain were assessed using a SEM scanner, thermography imaging, skin hydration device and numeric pain intensity scale, respectively. Measurements were taken at the sacrum, both heels and a control site, before and after surgery for 3 days. Data were analysed using Pearson or Spearman's correlation. Of the participants, 50% were male with a mean age of 58 years (±13.46). Low positive/negative correlations between SEM and temperature were found at the sacrum. However, after removing outliers, these results were not statistically significant. Other sites and follow-up days showed negligible correlations. No evidence of a correlation, to low correlations between SEM and EH were observed, but unreliable due to little variation in EH at the heels. Pain showed negligible correlations with SEM. This study did not find consistent evidence of a correlation between SEM, temperature, EH and pain, highlighting the unreliability of temperature and EH for early PU detection. Post-operative pain may also confound accurate pain assessments.

A Bayesian competing risk analysis of renal cancer patients based on SEER database.

BACKGROUND: Renal cell carcinoma (RCC) remains a global health concern due to its poor survival rate. This study aimed to investigate the influence of medical determinants and socioeconomic status on survival outcomes of RCC patients. We analyzed the survival data of 41,563 RCC patients recorded under the Surveillance, Epidemiology, and End Results (SEER) program from 2012 to 2020. METHODS: We employed a competing risk model, assuming lifetime of RCC patients under various risks follows Chen distribution. This model accounts for uncertainty related to survival time as well as causes of death, including missing cause of death. For model analysis, we utilized Bayesian inference and obtained the estimate of various key parameters such as cumulative incidence function (CIF) and cause-specific hazard. Additionally, we performed Bayesian hypothesis testing to assess the impact of multiple factors on the survival time of RCC patients. RESULTS: Our findings revealed that the survival time of RCC patients is significantly influenced by gender, income, marital status, chemotherapy, tumor size, and laterality. However, we observed no significant effect of race and origin on patient's survival time. The CIF plots indicated a number of important distinctions in incidence of causes of death corresponding to factors income, marital status, race, chemotherapy, and tumor size. CONCLUSIONS: The study highlights the impact of various medical and socioeconomic factors on survival time of RCC patients. Moreover, it also demonstrates the utility of competing risk model for survival analysis of RCC patients under Bayesian paradigm. This model provides a robust and flexible framework to deal with missing data, which can be particularly useful in real-life situations where patients information might be incomplete.

The correlation between sub-epidermal moisture measurement and other early indicators of pressure ulcer development-A prospective cohort observational study. Part 1. The correlation between sub-epidermal moisture measurement and ultrasound.

The correlation between sub-epidermal moisture (SEM) and other early indicators of pressure ulcer (PU) development is yet to be determined. This three-part series aims to bridge this knowledge gap, through investigating SEM and its correlation with evidence-based technologies and assessments. This article focuses on the correlation between SEM and ultrasound. A prospective cohort observational study was undertaken between February and November 2021. Patients undergoing three surgery types were consecutively enrolled to the study following informed consent. Assessments were performed prior to and following surgery for 3 days at the sacrum, both heels and a control site, using a SEM scanner and high-frequency ultrasound scanner (5-15 MHz). Spearman's rank (rs ) explored the correlation between SEM and ultrasound. A total of 60 participants were included; 50% were male with a mean age of 58 years (±13.46). A statistically significant low to moderately positive correlation was observed between SEM and ultrasound across all anatomical sites (rs range = 0.39-0.54, p < 0.05). The only exception was a correlation between SEM and ultrasound on day 0 at the right heel (rs = 0.23, p = 0.09). These results indicate that SEM and ultrasound agreed in the presence of injury; however, SEM was able to identify abnormalities before ultrasound.

Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome.

AIMS: Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. METHODS AND RESULTS: This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1ß. Circulating plasma levels of interleukin-1ß decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. CONCLUSION: This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.

Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis.

INTRODUCTION: Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 -174 G/C, rs1800795) have been shown to be independently associated with coronary artery disease (CAD) by several investigators. Despite more than 12 published meta-analyses on this subject, association of -174 G/C with CAD, especially amongst distinct ancestral population groups remain unclear. We, therefore, conducted a systematic review and an updated meta-analysis to comprehensively ascertain the association of IL6 -174 G/C with CAD and circulating IL-6 levels. MATERIALS AND METHODS: Relevant case-control/cohort studies investigating association of -174 G/C with CAD and circulating IL-6 levels were identified following a comprehensive online search. Association status for CAD was determined for the pooled sample, as well as separately for major ancestral subgroups. Association status for circulating IL-6 levels was assessed for the pooled sample, as well as separately for CAD cases and CAD free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled using random/fixed-effects model. RESULTS: Quantitative synthesis for the CAD endpoint was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases/32,053 controls). Pooled association of -174 G/C with CAD was found to be statistically significant through dominant (OR 1.15; 95% CI 1.05-1.25, p = 0.002) as well as allelic genetic model comparisons (OR 1.13, 95% CI 1.06-1.21, p = 0.0003). This effect was largely driven by Asian and Asian Indian ancestral subgroups, which also showed significant association with CAD in both genetic model comparisons (OR range 1.29-1.53, p value range ≤ 0.02). Other ancestral subgroups failed to show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the 'C' allele carriers in the pooled sample (Standard mean difference, SMD 0.11, 95% CI 0.01-0.22 pg/ml, p = 0.009) as well as in the CAD free control subgroup (SMD 0.10, 95% CI 0.02-0.17 pg/ml, p = 0.009), though not in the CAD case subgroup (SMD 0.17, 95% CI = - 0.02 to 0.37, p = 0.12). CONCLUSIONS: The present systematic review and meta-analysis demonstrate an overall association between IL6 -174 G/C polymorphism and CAD, which seems to be mainly driven by Asian and Asian Indian ancestral subgroups. Upregulation of plasma IL-6 levels in the 'C' allele carriers seems to be at least partly responsible for this observed association. This warrants further investigations with large, structured case-control studies especially amongst Asian and Asian Indian ancestral groups.

A review on ferulic acid and analogs based scaffolds for the management of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related multifactorial neurodegenerative disorder characterized by severe central cholinergic neuronal loss, gradually contributing to cognitive dysfunction and impaired motor activity, resulting in the brain's cell death at the later stages of AD. Although the etiology of AD is not well understood, however, several factors such as oxidative stress, deposition of amyloid-ß (Aß) peptides to form Aß plaques, intraneuronal accumulation of hyperphosphorylated tau protein, and low level of acetylcholine are thought to play a major role in the pathogenesis of AD. There is practically no drug for AD treatment that can address the basic factors responsible for the neurodegeneration and slow down the disease progression. The currently available therapies for AD in the market focus on providing only symptomatic relief without addressing the aforesaid basic factors responsible for the neurodegeneration. Ferulic acid (FA) is a phenol derivative from natural sources and serves as a potential pharmacophore that exerts multiple pharmacological properties such as antioxidant, neuroprotection, Aß aggregation modulation, and anti-inflammatory. Several FA based hybrid analogs are under investigation as a multi-target directed ligand (MTDLs) to develop novel hybrid compounds for the treatment of AD. In the present review article, we are focused on the critical pathogenic factors responsible for the onset of AD followed by the developments of FA pharmacophore-based hybrids compounds as a novel multifunctional therapeutic agent to address the limitations associated with available treatment for AD. The rationale behind the development of these compounds and their pharmacological activities in particular to their ChE inhibition (ChEI), neuroprotection, antioxidant property, Aß aggregation modulation, and metal chelation ability, are discussed in detail. We have also discussed the discovery of caffeic and cinnamic acids based MTDLs for AD. This review paper provides an in-depth insight into the research progress and current status of these novel therapeutics in AD and prospects for developing a druggable molecule with desired pharmacological affinity and reduced toxicity for the management of AD.

Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19.

The importance of the main protease (Mpro) enzyme of SARS-CoV-2 in the digestion of viral polyproteins introduces Mpro as an attractive drug target for antiviral drug design. This study aims to carry out the molecular docking, molecular dynamics studies, and prediction of ADMET properties of selected potential antiviral molecules. The study provides an insight into biomolecular interactions to understand the inhibitory mechanism and the spatial orientation of the tested ligands and further, identification of key amino acid residues within the substrate-binding pocket that can be applied for structure-based drug design. In this regard, we carried out molecular docking studies of chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV), GS441524, arbidol (ARB), and natural product glycyrrhizin (GA) using AutoDock 4.2 tool. To study the drug-receptor complex's stability, selected docking possesses were further subjected to molecular dynamics studies with Schrodinger software. The prediction of ADMET/toxicity properties was carried out on ADMET Prediction™. The docking studies suggested a potential role played by CYS145, HIS163, and GLU166 in the interaction of molecules within the active site of COVID-19 Mpro. In the docking studies, RDV and GA exhibited superiority in binding with the crystal structure of Mpro over the other selected molecules in this study. Spatial orientations of the molecules at the active site of Mpro exposed the significance of S1-S4 subsites and surrounding amino acid residues. Among GA and RDV, RDV showed better and stable interactions with the protein, which is the reason for the lesser RMSD values for RDV. Overall, the present in silico study indicated the direction to combat COVID-19 using FDA-approved drugs as promising agents, which do not need much toxicity studies and could also serve as starting points for lead optimization in drug discovery.

"Laparoscopic Cholecystectomy: A Single Surgeon's Experience in some of the Teaching Hospitals of West Bengal".

Laparoscopic cholecystectomy has revolutionized the management of symptomatic gallstone disease since its introduction more than 20 years ago. It has gained widespread acceptance and is presently the gold standard for its management. This large study spanned over last 10 years and includes prospective data on 950 elective cases of laparoscopic cholecystectomy since 2002. All cases were operated personally by the author in different teaching hospitals of West Bengal. The following were looked into: profiles of the patients including major comorbidities requiring special precautions, the frequency of "difficult cholecystectomies," conversion rate, and operative and postoperative complications. The results showed that 75 % of the patients were females. The mean age of the female patients was 35 years (range15-75), while that of the male patients was 42 (range 18-68). Thirty-two patients had major comorbidities which required special precautions in the perioperative period. Twenty-six percent of the cases were categorized as "difficult," and 6 % of the cases had to be converted to open procedure. Major complications occurred in 11 patients of which five had to be converted. Fifty-five patients had port-site infection due to atypical mycobacteria species of which majority occurred in the last 1 year of the study. All of them responded to second-line antitubercular medications.

Differential release kinetics of cardiac biomarkers in off-pump coronary bypass.

BACKGROUND: Differential release kinetics of the cardiac biomarkers (B-type natriuretic peptide, troponin I, and creatine kinase-MB) following off-pump coronary artery bypass are not well characterized. METHODS: Biomarker levels were assessed at 6, 24, 48 h, and 1 month preoperatively, in 80 patients who underwent off-pump coronary artery bypass. RESULTS: All biomarkers increased within 6 h of surgery. Peak B-type natriuretic peptide levels occurred at 24-48 h in 96% of patients, but only two-thirds had peak troponin I and creatine kinase-MB levels at this time, reflecting different release patterns. Levels of all biomarkers declined within 48 h, but 42% of patients still had B-type natriuretic peptide >100 pg·mL(-1) at 1 month. Those with baseline B-type natriuretic peptide > 100 pg·mL(-1) had a lower left ventricular ejection fraction (43.6% vs. 55.6%, p < 0.01) and longer inotropic (43.8 vs. 31.4 h, p = 0.03) and ventilator support (34 vs. 25.5 h, p = 0.04) than those with lower levels. B-type natriuretic peptide levels correlated positively with angiographic Syntax score (p = 0.02) and negatively with left ventricular ejection fraction (p < 0.001). Only baseline B-type natriuretic peptide predicted the durations of inotropic support (p = 0.01) and ventilation (p = 0.02). Postoperative B-type natriuretic peptide at 6, 24, and 48 h and delta B-type natriuretic peptide were significant predictors of mean ventilation time. CONCLUSION: Even in patients undergoing off-pump surgery, there is significant natriuretic peptide and myocardial enzyme release. Only B-type natriuretic peptide levels had an association with postoperative variables.

Differential Release Kinetics of Cardiac Biomarkers in Patients Undergoing Valve Replacement Surgery.

BACKGROUND: Differential release kinetics of cardiac biomarkers including brain natriuretic peptide (BNP), Troponin-I, and CK-MB following valve replacement (VR) are not well characterized. METHODS AND RESULTS: We serially measured these biomarkers 24 hours prior, six hours, 24 hours, 48 hours, and one month following mitral/aortic VR in 100 patients. Baseline BNP, Tn-I, and CK-MB levels were 304.01 pg/mL, 0.03 ng/mL, and 0.99 ng/mL, respectively. While BNP levels decreased at six hours, and then peaked at 24 hours, Tn-I and CK-MB levels increased within six hours and then showed declining trends by 24 hours. While Tn-I and CK-MB levels normalized at one month, 33% patients still had BNP >200 pg/mL. Those with baseline BNP >200 pg/mL more commonly had AF, higher RV systolic pressure, longer inotrope and ventilator duration, and longer mean ICU/hospital stay as compared to those with lower BNP, although echocardiographic left ventricular ejection fraction and Tn-I/CK-MB levels were similar. Inotrope duration >42 hours, ventilation time >29 hours, and ICU stay >4 days was seen in 42% versus 19%, 30% versus 9%, and 33% versus 14%, respectively, in those with BNP >/<200 pg/mL. Baseline BNP had a significant positive correlation with mean inotrope duration, ICU, and hospital stay. Baseline BNP was also a significant predictor of inotrope duration (odds ratio [OR]=5.9, 95% confidence interval [CI]=1.20-29.68, p=0.01) and ventilation time (OR=4.7, 95% CI=1.76-17.21, p=0.02). CONCLUSION: Release kinetics of cardiac biomarkers is significantly different following VR; BNP levels increase following an initial transient decline. Only BNP was a predictor of postoperative variables.

Lack of association between Glu298Asp polymorphism and coronary artery disease in North Indians.

Nitric Oxide (NO) is an important molecule carrying number of different functions in humans. Published studies suggest that it may inhibit several key steps involved in the pathogenesis of atherosclerosis. Inhibition or reduction of NO due to Glu298Asp polymorphism may accelerate atherosclerosis. The aim of this study was to determine whether Glu298Asp polymorphism is implicated in the pathogenesis of coronary artery disease (CAD) among North Indian population from the state of Uttar Pradesh, India. We selected 253 CAD patients and 174 healthy, normotensive, non-diabetic controls, which were matched for gender and ethnicity. The Glu298Asp (rs1799983) variant was detected by genotyping subjects, using a polymerase chain reaction followed by restriction fragment length polymorphism. There was no significant difference found in the genotypic and allelic frequencies between patients and controls. Our study indicated that Glu298Asp polymorphism does not play any critical role in the pathogenesis of CAD, at least in North Indian population.

Morphological and ultrastructural characteristics of extracellular matrix changes in oral squamous cell carcinoma.

BACKGROUND: The biology of oral squamous cell carcinoma (OSCC), including its progression from dysplasia to carcinoma, "field effects", genetic changes in tumor associated mucosa (TAM) and effect of matrix metalloproteinases in breaking down of matrix proteins to facilitate invasion, has been well documented. However, what remains to be done is to extrapolate this knowledge to improve patient care. AIM: The aim of this study was to observe the extracellular matrix (ECM) changes with the routine histochemical stains available to most histopathologists. MATERIALS AND METHODS: The study includes 72 cases of OSCC in which the tumor and adjacent normal appearing areas were sampled to study the ECM changes with hematoxylin and eosin (H and E) and Verhoeff's-Van Gieson elastic stain (VVG). RESULTS: Basophilic fragmentation of collagen (H and E) and clumped short elastic fibers (VVG) were seen in 12 (16.7%) cases. Of the remaining cases, 18 (25%) had a dense lymphocytic infiltrate and had no demonstrable elastic fibers. Those cases with H and E changes were further studied and compared with normal mucosa for ultrastructural changes. The ultrastructural study demonstrated an increase in oxytalan, elaunin and elastic fibers and decrease in collagen fibers with some transformation changes associated with OSCCs and lymph node metastasis. CONCLUSION: Changes in transformation of collagen to elastic fibers and also the loss of both the fibers in areas of lymphocytic infiltration possibly indicate degradation of ECM fibers by factors released from the lymphocytes or tumor cells and the limiting effect on the tumor by ECM remodeling.

Spontaneous perforation of common bile duct: a rare complication of choledocholithiasis.

A 35-year-old female presented with 48 hrs history of severe upper abdominal pain and abdominal distension. The patient was suffering from intermittent episodes of colicky upper abdominal pain and spiky fever with chill and rigor in association with yellowish discoloration of eyes and urine for last 3 months. On examination the lady was dehydrated, icteric, febrile and was having tachycardia and hypotension. Abdominal examination indicated features of generalized peritonitis. Hematological profile suggested neutrophilic leukocytosis, blood biochemistry suggested conjugated hyperbilirubinemia, raised alkaline phosphatase and transaminases. Skiagram of the abdomen showed ground glass opacity without any free gas under the diaphragm. Ultrasonography and contrast enhanced CT scan of the abdomen revealed multiple calculi within a distended, thick walled gall bladder, dilated common bile duct (CBD) with a 12.8 mm stone impacted at its lower end and free fluid in the lesser sac and rest of the peritoneal cavity. Diagnostic abdominal paracentasis showed heavily bile stained fluid. Exploration done for generalized biliary peritonitis with sepsis, revealed erosion at the posterior aspect of the retro-duodenal CBD over the site of the impacted stone. She underwent cholecystectomy, choledocholithotomy through a supra-duodenal choledochotomy, and T-tube drainage of the CBD. She made a slow but steady post operative recovery and was discharged from the hospital after 22 days in favorable conditions.

Mesenteric cyst: an unusual presentation.

A 5-year-old boy presented with the history of a small lower abdominal swelling since childhood which increased in size and became painful following a fall. Examination revealed a mobile, globular, cystic intraabdominal mass in the lower abdomen. Ultrasonography of the abdomen suggested a 7.5 × 5.5 cm cystic lesion, separate from the bladder, containing an echogenic mobile mass. Intra venous urography excluded any abnormality of the kidneys, ureters and bladder. Exploratory laparotomy revealed a sigmoid mesenteric cyst protruding out of one of the mesenteric leaves and attached to it by a narrow stalk. The excised cyst was found to be thin walled and unilocular. It was internally lined with fibrinous exhudate and contained serous fluid and a solid spherical blood clot. The child had an uneventful postoperative recovery. Histopathology of the cyst wall showed maturing granulation and fibrous tissue with hemosiderin laden macrophages and lymphoid aggregates consistent with the diagnosis of a lymphagioma with chronic inflammatory changes and evidence of past hemorrhage.